Bone Marrow Mesenchymal Stem Cell‐Derived Exosomal miR‐4787‐3p Promoted Osteogenic Differentiation by Targeting PDCD4 in Osteonecrosis of Femoral Head

Dec 30, 2025Journal of biochemical and molecular toxicology

Bone Marrow Stem Cell Exosomes Carrying miR-4787-3p May Help Bone Cell Growth by Targeting PDCD4 in Hip Bone Death

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Abstract

Exosomal miR-4787-3p from bone marrow mesenchymal stem cells may enhance osteogenic differentiation in BMSCs associated with osteonecrosis of the femoral head.

Impaired osteogenic differentiation is identified as a key mechanism in osteonecrosis of the femoral head.
miR-4787-3p levels were found to be lower in exosomes derived from patients with traumatic ONFH compared to healthy donors.
Treatment with exosomal miR-4787-3p improved BMSC viability and promoted osteogenic differentiation, indicated by increased mineralization and ALP activity.
PDCD4 was confirmed as a target of miR-4787-3p and was more highly expressed in BMSCs from patients with traumatic ONFH.
Knockdown of PDCD4 in BMSCs led to enhanced viability and increased markers of osteogenic differentiation.
Exosomal miR-4787-3p's effects on BMSCs' osteogenic differentiation may be mediated through the inhibition of PDCD4.

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Impaired osteogenic differentiation serves as a pivotal pathogenic mechanism underlying osteonecrosis of the femoral head (ONFH). This study systematically investigated the pro-osteogenic effects of exosomal miR-4787-3p derived from bone marrow mesenchymal stem cells (BMSCs) in the pathogenesis of ONFH. Bone marrow was collected from both healthy donors and patients with post-traumatic ONFH. BMSC and BMSC-derived exosomes were isolated and characterized. BMSCs were transfected with miR-4787-3p mimic and inhibitor to collect exosomes. These exosomes were used to treat BMSCs stimulated by dexamethasone (DEX). A dual luciferase reporter gene assay was employed to verify the binding of miR-4787-3p and programmed cell death 4 (PDCD4). BMSCs were transfected with PDCD4 shRNA and stimulated by DEX. BMSCs transfected by PDCD4 vectors were stimulated by exosomes and DEX. Cell counting kit-8 assay, Alizarin red staining, and ALP activity detection were performed on BMSCs. Molecular analyses included qRT-PCR and Western blot of osteogenic markers and PDCD4 signaling components. BMSC and BMSC-derived exosomes were successfully isolated. Relative to healthy donors, miR-4787-3p was downregulated in BMSC-derived exosomes from patients with traumatic ONFH. Exosomal miR-4787-3p enhanced BMSCs' viability and osteogenic differentiation, as evidenced by increased mineralization, ALP activity, and upregulation of ALP/OPN/Runx2. PDCD4 was a target of miR-4787-3p. PDCD4 was up-modulated in BMSCs from patients with traumatic ONFH. PDCD4 knockdown enhanced BMSCs' viability, Alizarin red staining, ALP activity, ALP, OPN and Runx2 expression. PDCD4 reversed BMSC-derived exosomal miR-4787-3p promotion on BMSCs' viability, Alizarin red staining, ALP activity, ALP, OPN and Runx2 expression. BMSC-derived exosomal miR-4787-3p promoted BMSCs' osteogenic differentiation through direct targeting of PDCD4. These findings suggest its potential therapeutic application for ONFH by reversing impaired osteogenesis.

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Bone Marrow Mesenchymal Stem Cell‐Derived Exosomal miR‐4787‐3p Promoted Osteogenic Differentiation by Targeting PDCD4 in Osteonecrosis of Femoral Head

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